OBJECTIVE To explore the possible role of NO in aging in a rhesus macaque model. RESULTS A trend for somewhat lower NO concentrations was found in older, postmenopausal monkeys, while circulating levels of NO did not seem to be influenced by age or long-term dietary restriction in male rhesus monkeys. DISCUSSION Nitric oxide (NO) has been proposed to play a role in the aging process and to be relatively low during menopause. Dietary restriction (DR) retards aging and increases lifespan in rodents, and it has recently been shown to have beneficial effects on health in rhesus and cynomolgus macaques. In order to explore the possible role of NO in aging in this nonhuman primate model, we measured circulating levels of NO in group of premenopausal (n=9; aged 12.610.3 years [mean1SEM]) and postmenopausal (n=10; aged 26.810.4 years) female rhesus monkeys, young adult (n=9; aged 11.910.5 years) and old (n=10; aged 26.711.0 years) male rhesus monkeys, and in male rhesus monkeys (16-22 years old) that had undergone 30% DR for 8 years (n=12) and their matched control group fed ad libitum (n=12). Premenopausal monkeys had marginally higher serum NO concentration than postmenopausal monkeys 37.8912.79 5M vs. 31.2312.66 5M, respectively, p=0.099. In contrast, young adult male macaques did not differ from older males in serum NO concentration 37.8414.39 5M vs. 37.1714.84 5M, respectively. Also, plasma NO values did not differ between control and restricted male monkeys 34.0814.17 5M vs. 33.6512.88 5M, respectively. The trend for somewhat lower NO concentrations in the older, postmenopausal monkeys merits further investigation. On the other hand, circulating levels of NO do not seem to be influenced by age or by long-term DR in male rhesus monkeys. These results do not preclude an important role for localized, i.e., tissue specific, NO influences on the myriad physiological changes that occur during the menopausal transition and as a consequence of DR. FUTURE DIRECTIONS We plan to further investigate the relationship and significance of circulating NO in relation to the menopausal transition and dietary restriction. KEY WORDS Dietary restriction, aging, menopause FUNDING NIH PO1 AG11915